Benzimidazole derivatives protect against cytokine-induced apoptosis in pancreatic β-Cells

• Published in: Bioorganic and Medicinal Chemistry Letters
• Main Author: Zawawi N.K.N.A.; Rajput S.A.; Taha M.; Ahmat N.; Ismail N.H.; Abdullah N.; Khan K.M.; Choudhary M.I.
• Format: Article
• Language: English
• Published: Elsevier Ltd 2015
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84942987379&doi=10.1016%2fj.bmcl.2015.08.022&partnerID=40&md5=b80c7d05ba658efaf96478c151982819

Apoptotic cell death is the cause of the loss of insulin-producing β-cells in all forms of diabetes mellitus. The identification of small molecules capable of protecting cytokine-induced apoptosis could form the basis of useful therapeutic interventions. Here in, we present the discovery and synthesis of new benzimidazole derivatives, capable of rescuing pancreatic β-cells from cytokine-induced apoptosis. Three hydrazone derivatives of benzimidazole significantly increased the cellular ATP levels, reduced caspase-3 activity, reduced nitrite production and increased glucose-stimulated insulin secretion in the presence of proinflammatory cytokines. These findings suggest that these compounds may protect β-cells from the harmful effects of cytokines and may serve as candidates for therapeutic intervention for diabetes. © 2015 Elsevier Ltd. All rights reserved.